[EFFECT OF VOLUNTARY BREATH-HOLDING AND COGNITIVE LOADS ON REGIONAL CEREBRAL BLOOD FLOW AND BIOELECTRIC ACTIVITY OF THE BRAIN].

Cerebral blood flow and bioelectric activity were studied in 10 normal volunteers in order to assess cerebrovascular reactivity during different types of functional testing. The transcranial Doppler was used to measure linear blood velocity (LBV) in the middle cerebral artery (MCA) during maximal voluntary breath-holding (apnea), controlled verbal association test and tactile memory test. Simultaneous electroencephalography (EEG) registered the bioelectric activity of the brain cortex. Both investigations were performed continuously in the course of each test. Breath-holding induced a smooth symmetric increase of CMA blood velocity; LBV rose to maximum values in the majority of the volunteered subjects. Two subjects with small focal changes in the brain's white matter displayed an asymmetric blood flow reaction to apnea. Gain in LBV was materially less during the cognitive tests; the verbal test decreased LBV in one half of the subjects and increased LBV in the other. The tactile memory test increased LBV which was particularly high in the left CMA of all subjects. LBV dynamics during the cognitive tests was essentially different from what was observed in apnea. Blood flow variations in the course of equally the verbal and tactile tests had a regular undulatory character. Concurrent LBV and EEG monitoring made it possible to compare and contrast dynamics of the cerebral blood velocity and bioelectric activity directly during testing and thus to reveal peculiar reactions of the cerebral blood flow to cognitive and physiological testing.

[Effects of the 520-day isolation on the functional state of the cardiovascular system].

Purpose of the work was to study the cardiovascular effects of simulated factors in a 520-day crewed mission to Mars, and to validate the diagnostic value of the ultrasonic investigation of microcirculation and endothelium-dependent dilation of the right brachial artery in 6 male volunteers at the age of 28 to 39 years. It appears that 520-d isolation affected intracardiac hemodynamics and endothelium function more dramatically compared with 105-d isolation, increasing the risk of atherosclerosis. These findings add insight into the "cost of human adaptation" to very long isolation.

[Evaluation of the radiofrequency ablation effectiveness in patients with the Wolff-Parkinson-White syndrome].

A one-year prospective study involved 22 patients with the Wolff-Parkinson-White syndrome (WPW) and 20 healthy people. Means age of patients was 34.3 +/- 16.3 years. All 22 patients were successfully treated with radiofrequency ablation (RFA) of additional pathways. RFA effectiveness was evaluated with the help of clinical questionnaire, data of ECG, EchoCG, heart rate variability (HRV), frequency response and nonlinear dynamics. Cardiac rhythm disturbances were verified using Holter monitoring applied to all patients. Positive clinical effect was achieved in all the WPW patients, as RFA arrested cardiac arrhythmias completely. Holter monitoring did not register cardiac disturbances which points to high RFA effectiveness in WPW patients. HRV, frequency response and nonlinear dynamics reassumed their normal patterns.

[Scatological investigations during 105-day isolation].

Dynamics of the gastrointestinal functioning was reconstructed by analysis of the scatological data from volunteered subjects before, on days 16, 35, 45, 60, 90 and after completion of 105-day isolation experiment. The analysis showed that scatological investigations performed in the conditions imitating life in an exploration vehicle environment are instrumental in detecting deviations in the GI function indicative of pancreas excretory and hepar biliary excretion and synthetic hypofunction that can be responsible for intestinal dysfunction. Normalization of scatological parameters following the experiment witnesses to functional genesis of the changes observed during the exploration mission simulation.

[Investigation of cardiovascular adaptation to postural passive test in the course of selecting candidates for special contingent].

Selection of candidates for special contingent is made with the focus on evaluation of cardiovascular functioning and adaptability to stresses, and detection of pre-disease shifts in CV regulation. Hemodynamics regulation was assessed by tilt testing of 15 essentially healthy men at the age of 18 to 34. The tilt table was initially at 0 degrees (baseline), turned at +75 degrees (20 min), and then back to 0 degrees for 5-min recovery. Simultaneously with the standard measurements of ECG and blood pressure, the myocardium state was registered with the use of KardioVizor-06; cerebral circulation was evaluated using rheoencephalography and microcirculation vessels, -ultrasonic Doppler. Three human subjects exhibited hypotensive reactions to the tilt test and two showed hypertensive reactions. However, no changes were present on ECG records. Hence, in-depth investigation of the CV reaction to tilt test is capable to reveal incipient regulatory disorders and their trend, and to assess adaptability to stresses.

[Screening-diagnostics of the myocardium during test-loading on bicycle ergometer].

Diagnostic and prognostic potentiality of KardioVizor-06 (KV) in early detection of deviations in the myocardium electrophysiological parameters was assessed with the standard functional test on bicycle ergometer. The investigation was performed with participation of 10 essentially healthy subjects of different age groups. Data obtained with KV (baseline, test and recovery) were compared and contrasted with the results of standard ECG (12 leads) and BP methods. Data agreement was observed in 90% of cases; KV undervalued test tolerance in 10% of cases. Close examination of ECG verified the presence of incipient deviations in the myocardium. Therefore, unlike other methods, the technology provides unique information and foretells pathology discerning transient functional disorders. High noise immunity of the automated analysis of ECG dispersing changes makes the device applicable directly during functional loading tests.

[New approaches to diagnostics and identification of possible damages in normal humans under the conditions of microgravity and exposure to low doses of radiation].

The issues of radiation risk evaluation were addressed in the investigation of cytogenetic and molecular-biological changes in lymphocytes of cosmonauts and pilots of high-altitude airplanes. The goal was to determine individual sensitivity to the flight conditions and an additional factor (lymphocyte exposure to 1 Gy in situ), and adaptability as an index of induction of cell and organism resistance to extreme conditions.

[Individual cytogenetic and molecular-biological characteristics of lymphocytes in blood of pilots and cosmonauts].

The purpose of this paper was the investigation of the pilots and of cosmonauts individual sensitivity to the fly conditions, to the additional irradiation (in the dose of 1 Gy), the adaptive response manifestation (in the doses 0.05 and 0.5 Gy). The DNA comet assay (the double strand DNA breaks was determined) and the method of unstable chromosome aberrations in metaphase was used. The human blood lymphocytes was the object of investigation. The significant individual differences were discovered in pilots and in cosmonauts in the initial DNA damage; in the sensitivity to the additional irradiation. The frequency of the adaptive response induction was decreased in the pilots in the comparison with the control group. The adaptive response was registered in cosmonauts (3 men). It is supposed that DNA damage, chromosome aberrations, sensitivity to the additional irradiation, the adaptive response manifestations can be used as biological markers of individual risk disease.

[Population genetic study of Russian cosmonauts and test subjects: genetic demographic parameters and immunogenetic markers].

Genetic demographic characteristics and immunogenetic markers (blood groups ABO, Rhesus, MNSs, P, Duffy, Kidd, and Kell) have been studied in a group of 132 Russian cosmonauts and test subjects (CTSG). Analysis of pedigrees has shown a high exogamy in the preceding generations: almost half of the subjects have mixed ethnic background. According to the results of genetic demographic analysis, a sample from the Moscow population was used as control group (CG). Comparison between the CTSG and CG has demonstrated significant differences in genotype frequencies for several blood group systems. The CTSG is characterized by a decreased proportion of rare interlocus genotypic combinations and an increased man heterozygosity. Analysis of the distributions of individual heterozygosity for loci with codominant expression of alleles has shown that highly heterozygous loci are more frequent in the CTSG. Taking into account that the CTSG has been thoroughly selected from the general population, it is concluded that heterozygosity is related to successful adaptation to a space flight.

[Identification of individual genotype parameters, informative for medical care in piloted space missions: modern and future capabilities].

The factors of space flight provoke some negative shifts in crew health. Improvement of the methods of diagnostics, evaluation of predisposition to diseases and correction of functional deviations is within the scope of the crew medical operations personnel. It is also a new focus of biomedical research referred to as "personalized medicine" the corner stone of which is genetic analysis. Investigations in this area are prediscovery by character; population genetics seems to be the most adequate approach. The authors give examples of candidate genes the genotypes of which could be of significance to medical operations and discuss the genetic safety of space flight. Aside from the applied aspects, the genetic investigations of space crews are of their own concernment in understanding the genetic basis of differences in biological resistance to unhealthy environment.

[Effect of space flight factors on health of cosmonauts in the near and late term after space flights]. / Izuchenie vliianiia faktorov kosmicheskogo poleta na zdorov'e kosmonavtov v blizhaishie i otdalennye sroki posle kosmicheskikh poletov.

Cytogenetical studies of cosmonauts' peripheral blood lymphocytes after space flights on MIR orbital station showed a statistically significant increase in the yields of radiation-induced chromosomal aberrations. However, similar studies with in vitro irradiation of biological objects with accelerated charged particles are of great importance for elucidation of the nature of cytogenetical damage induced in vivo. It is also important to investigate the structure of cosmonatus' diseases over their life, in particular, lens opacities and oncological diseases. Thus, the purpose of the investigations planned is to study cytogenetical damage in blood lymphocytes from cosmonauts after space flights on the ISS in vivo, as well as in donor blood lymphocytes after in vitro exposure to accelerated charged particles. The tasks of the project are as follows: determination of the yields and types of chromosomal aberrations in cosmonauts' blood lymphocytes before and after space flights, comparative studies of biological effects induced in vitro by different types of ionizing radiation in human blood lymphocytes in ground experiments, assessment of cytogenetical risks, analysis of the structure of cosmonatus' diseases comparing with that of whole population, study of the mortality and frequency of cataracts and oncological diseases in cosmonauts. The results to be obtained will be used for setting of health norms applied to the influence of radiations of different types, and for elaboration of measures to reduce health risks from space flight factors.

[Distribution of creatine phosphokinase isoenzymes (EC 2.7.3.2) in cardiac cells]. / Raspredelenie izofermentov kreatinfosfokinazy (EC 2.7.3.2) v serdechnykh kletkakh

The distribution of the creatinephosphokinase isoenzymes in the cardiac cells was studied by way of fractional extraction combined with an electrophoretic analysis of each of the received fractions. At the same time, the content of the creatinephosphokinase isoenzymes was studied in carefully purified preparations of myofibrils and mitochondria. The results of the conducted analysis indicate a heterogenic distribution of the creatinephosphokinase isoenzymes within the cells: about 30% of the cellular activity of the enzyme is contained in the mitochondria (the mitochondrial isoenzyme) 50% is comprised by the fraction dissolved in the cytoplasm (isoenzymes MM, MB and BB), and about 20%--in the myofibrils (isoenzyme MM), 5% of them being extracted only by a 0.9 M KCl solution. The myofibril preparation freed of the mitochondria also contains some important creatinephosphokinase activity (isoenzyme MM) comparable with their ATP-ase activity. The mitochondrial isoenzymes is found only in these structures of the cell.

[Study of the role of mitochondrial creatine phosphokinase isoenzyme in the process of energy transport in cardiac cells]. / Izuchenie roli mitokhondrial'nogo izofermenta kreatinfosfokinazy v protsesse perenosa energii v serdechnykh kletkakh

The kinetic properties of creatinephosphokinase connected with the mytochondria of the heart were studied. The following kinetic parameters were measured: the Michaelis constants for all substrates -- MgATP, MgADP, creatine and creatinephosphate, and the maximal reaction rates for the direct and reverse reactions catalized by the mytochondrial iso-enzyme of creatinephosphokinase. The peculiarity of this iso-enzyme was demonstrated to consist in the independence of binding adeninenucleotides and guanidine substrates. The kinetic characteristics of this iso-enzyme are such that ATP synthesis from ADP and creatinephosphate is preferable: the Michaelis constant for MgADP is 0.05 mM, for creatinephosphate -- 0.5 mM, for MgATP -- 0.7 mM, for creatine -- 5.0 mM. It was also demonstrated that in the presence of all substrates and products of the reaction the ratio of the speeds of the direct and reverse reactions is regulated by Mg ions: with a low concentration of Mg (below that of ATP) the reaction of creatinephosphate synthesis takes place, with the Mg concentration growing the speed of ATP synthesis increases. Thus, an increase of Mg concentration can, depending on the conditions of the reaction, result in its complete reversal. The regulatory role of Mg is also demonstrated for the case in which ATP is synthesized in the reaction of oxidative phosphorylation, creatinephosphokinase-controlled reaction.

[Clinico-experimental study of the possibility of the use of immobilized enzymes for local thrombolysis and thromboformation]. / Kliniko-éksperimental'noe izuchenie vozmozhnostei primeneniia immobilizovannykh fermentov dlia lokal'nogo tromboliza i tromboobrazovaniia.

Fibrinolysin immobilized by a solid polysaccharide carrier capable of controllable biodegradation is shown to exert a local effective thrombolyzing action. Certain results of clinical studies of immobilized streptase (streptodecase) are presented. They show essential advantages of the new preparation over the known native enzymes. Experiments with animals show that the immobilized thrombin may be applied in therapeutic embolization for the hemorrhage cessation.

[Use of the method of thoracic electric bioimpedance in medical evaluation of central hemodynamics in man]. / Primenenie metoda grudnogo élektricheskogo bioimpedansa v ékspertnoi otsenke tsentral'noi gemodinamiki cheloveka.

Stroke and minute cardiac volumes were simultaneously determined at rest in seven healthy male subjects aged 28-48 and 13 patients with various forms of partial insufficiency of the central hemodynamics with the use of thoracic electrical bioimpedance and Doppler echocardiography. The bio-impedance method employed IBM-compatible NCCOM3-R7. The Doppler echocardiograms were registered using TOSHIBA-50. Correlative analysis of the records was performed on 4 parameters, i.e. minute volume (MV), stroke volume (SV), cardiac index (CI), and stroke index (SI). In the group with partial insufficiency the correlation coefficient amounted to 0.89, 0.92, 0.81 and 0.92 for MV, SV, CI and SI, respectively. In healthy subjects the correlation coefficient made up 0.91, 0.90, 0.89 and 0.91 for MV, SV, CI and SI, respectively. In the combined group the correlation coefficient averaged 0.88, 0.92, 0.83 and 0.92 for MV, SV, CI and SI, respectively. These results allow to rate high the accuracy of thoracic electrical bio-impedance and recommend it for the program of medical selection and annual health check of occupational groups systematically exposed to extreme impacts.

[Sensitivity of the respiratory center to carbon dioxide during prolonged exposure of humans to gas environment with unchanging level of hypercapnia]. / Chuvstvitel'nost' dykhatel'nogo tsentra k uglekislomu gazu pri dlitel'nom nakhozhdenii cheloveka v gazovoi srede s neizmeniaiushchimsia urovnem giperkapnii.

Effects of moderate CO2 concentrations (2.2-3.2%) on external respiration were studied in a series of extended (30-d) continuous tests with volunteered human subjects. In one test, PCO2 in the gas mixture was maintained at 15-19 mm Hg (2.0-2.5%), in the other, at 20-23 mm Hg (2.7-3.0%). Partial pressure of oxygen was controlled at 144-152 mm Hg (19-20%) with the barometric pressure, temperature and humidity at the norm. As compared with the onset, at the end of the first test parameters of the external respiration were changed neither at rest nor during exercises. At the end of the second test, the minute pulmonary ventilation showed a steady rise in synch with the duration of exposure growing in 2.5 times at rest and in 1.7-2 times during physical exercises suggesting an increase in the respiratory center sensitivity to the CO2 level under study. Hence, breathing CO2 at 2.7-3.0% for many days did not sensitize the respiratory center of the human subjects.

[The influence of extended exposure in artificial hypercapnic environments on the function of external respiration and gas exchange]. / Vliianie dlitel'nogo nakhozhdenia v iskusstvennykh giperkapnicheskikh sredakh na funktsiiu vneshnego dykhaniia i gazoobmen.

Effects of artificial hypercapnic atmosphere were studied in a series of ten 40-d experiments with participation of 42 volunteers aged from 20 to 61 years. Partial pressure of carbon dioxide was maintained at 27 +/- 2 mm Hg (3.4-3.8% CO2); partial pressure of oxygen was in the range of 122-136 mm Hg. Barometric pressure, air temperature and humidity had normal values. Results of the experiments were subjected to the variation analysis. Continuous breathing the gas mixture with specified PCO2 increased CO2 sensitivity of the breathing center in all age-groups both at rest and during exercise. The ventilatory reaction of subjects aged 41-61 grew to a less degree as compared to the subjects below 40. Medical selection of members for space crew to go to a distant voyage should take into consideration the parameters of oxygen demand and the volume of pulmonary ventilation per a time unit.

[New approaches to diagnosis and correction of arterial hypertension in pilots and cosmonauts]. / Novye podkhody k diagnostike i korrektsii arterial'noi gipertenzii u pilotov i kosmonavtov.

One of the top priority goals of space medical operations is timely diagnostics of strained body regulation, particularly in the cardiovascular system, during space flight. Analysis of telemetric data allows foresee cardiovascular adaptation disturbance such as failure to stabilize arterial pressure and possible development of arterial hypertension aboard space vehicle, and delayed readaptation to 1-g after stay in microgravity. Demonstrated were interhemispheric differences, i.e. dominance of the right hemisphere in regulation of the cardiovascular system as a subsystem within the antigravity functional system, and the left hemisphere in circadian regulation of hemodynamics.

[Experience of selecting test-subjects for extended model studies]. / Opyt otbora ispytatelei dlia uchastiia v dlitel'nykh model'nykh issledovaniiakh.

Methodical approaches to selection and results of examination of test-subjects (aged 18 to 50 yr) volunteered to participate in extended model studies were reviewed. General and age-specific morbidity was analyzed. Various diseases (163 nosologic forms) were found in 94.3% of candidates. This fact raises concern since the age group of 18-50 represents the main employable cohort of population. Given rare visits of this age group to policlinic, the health service personnel should concentrate attention on prophylactic medical examination of "no-complaint" patients.